a tolerability and pharmacokinetics study of shr6390 in advanced melanoma patients

Conditions: Melanoma

Summary: shr6390 is a small molecular,oral potent, selective cdk4/6 inhibitor. the purpose of this study is to investigate the safety/tolerability and the pharmacokinetic profile of shr6390 in chinese advanced melanoma patients by using a "3+3" dose escalation.preliminary efficacy will be also investigated in this study.


Eligibility criteria:
inclusion criteria: * pathologically confirmed melanoma * unresectable stage iii or iv melanoma patient * companion with cell cycle pathway abnormal (e.g cdk4 amplify and/or ccnd1 amplify and/or cdkn2a loss) * eastern cooperative oncology group (ecog) performance status:0-1 * life expectancy ≥ 3 months * adequate function of major organs, meaning the following criteria should be met within 14 days before randomization: hemoglobin \> 100g/l neutrophils \> 2.0×10\^9/l platelets \> 100×10\^9/l total bilirubin \< 1.5×the upper limit of normal (uln) alt and ast ≤ 1.5×uln (≤ 5×uln, if existing liver metastases) creatinine ≤ 1 uln left ventricular ejection fraction (lvef) ≥ 50% qtcf(fridericia correction) male≤450 ms, female≤470 ms * good compliance of patient by physician's judgement * signed and dated informed consent exclusion criteria: * previously received therapy of anti-tumor agent targeting at cdk4/6 * less than 3 weeks from the last cell-toxicity chemotherapy, less than 6 weeks from last mitomycin or nitrosamine therapy * less than 3 weeks from any other anti-tumor therapy (including targets therapy, immunotherapy or other approved therapy) * having joined in other clinical trials within 4 weeks * uncontrolled/untreated brain metastasis (well-controlled/well-treated brain metastasis by physician's judgement is allowed) * existing abnormal ctcae≥grade 2 resulted from previous treatment * uncontrollable symptomatic pleural effusion or ascites or require clinical intervention * require continous treatment by steroids * factors influencing the usage of oral administration (e.g. unable to swallow, chronic diarrhea and intestinal obstruction, etc.) * existing uncontrollable hypokalemia or hypomagnesemia * history of serious allergy events or known being allergy constitution * active hbv or hcv infection (hbv virus≥10e4 copies/ml, hcv virus≥10e3 copies/ml) * history of immunodeficiency, acquired or congenital immunodeficiency, history of organ transplantation * history of cardiac dysfunction, include(1)angina (2)clinical significant arrythmia or require drug intervention (3)myocardial infarction (4)heart failure (5) other cardiac dysfunction (judged by the physician); any cardiac or nephric abnormal ≥grade 2 found in screening * female patients who are pregnancy, lactation or women who are of childbearing potential tested positive in baseline pregnancy test * childbearing female who refuse to accept any contraception practice * determined by the physician, any coexisting disease might lead to life threatening complications or avoid the patients from accomplishing the treatment(e.g serious hypertension, diabetes, thyroid dysfunction,etc.) * history of neuropathy or dysphrenia, including epilepsy and dementia

Keywords: melanoma cycline-dependent kinase